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Abstract  Glaucoma describes a group of diseases that kill retinal ganglion cells. There are different types of glaucoma, and each appears to be genetically heterogeneous. Different glaucoma genes have been identified, but these genes account for only a small proportion of glaucoma. Most glaucoma cases appear to be multifactorial, and are likely affected by multiple interacting loci. A number of genetic susceptibility factors have been suggested to contribute to glaucoma. These factors fit into two broad groups, those affecting intraocular pressure and those important in modulating retinal ganglion cell viability. Defining the complex genetics of glaucoma will require significant further study of the human disease and animal models. Genetic approaches are essential and will be enhanced by recently developed genomic and proteomic technologies. These technologies will provide valuable clues about pathogenesis for subsequent testing. In this review, we focus on endogenous genetic susceptibility factors and on how experimental studies will be valuable for dissecting the multifactorial complexity of their interactions.\u003C\u002Fjats:p>",{"EN":792},"COMPLEX GENETICS OF GLAUCOMA SUSCEPTIBILITY",{"VOID":794},"16124852",{"VOID":796},"10.1146\u002Fannurev.genom.6.080604.162209",[168],"https:\u002F\u002Fwww.annualreviews.org\u002Fdoi\u002F10.1146\u002Fannurev.genom.6.080604.162209",[800,833,855,898],{"id":801,"sortIndex":123,"researcher":24,"roles":802,"affiliations":803,"properties":826},"e3bcfc7b-1b9d-40c3-8460-6eb19ada8c05",[],[804,815],{"id":805,"sortIndex":25,"affiliation":806,"properties":24},"34b812bd-3aa6-49b8-9cae-11220eead58e",{"id":807,"createTime":808,"updateTime":809,"relativeEntities":810,"slug":811,"properties":812,"entityType":61,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"744f00b0-a8c0-4977-87e4-d9a411cc10a8","2023-12-05T06:36:04.695+00:00","2025-01-07T00:52:53.888+00:00",[],"Department-of-Physiology-and-Biophysics-University-of-Iowa-Iowa-City-Iowa-52242",{"title":813},{"VI":814},"Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242",{"id":816,"sortIndex":124,"affiliation":817,"properties":24},"d5b0454a-e4db-40f0-996f-6abb03b3cf26",{"id":818,"createTime":819,"updateTime":820,"relativeEntities":821,"slug":822,"properties":823,"entityType":61,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"d7daa1ad-a3d3-4dc4-8a7a-084d903f9847","2024-04-11T12:28:16.360+00:00","2024-12-11T16:20:31.116+00:00",[],"Jackson-Laboratory",{"title":824},{"EN":825},"Jackson Laboratory",{"openalex":827,"orcid":829,"title":831},{"VOID":828},"A5004162619",{"VOID":830},"https:\u002F\u002Forcid.org\u002F0000-0001-5730-6105",{"EN":832},"Michael G. 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Genet., 60, 296",{},{"id":24,"text":1556,"url":24,"identifiers":1557},"10.1001\u002Farchopht.117.2.237",{"doi":1556},{"id":24,"text":1559,"url":24,"identifiers":1560},"10.1016\u002Fj.tips.2004.03.002",{"doi":1559},{"id":24,"text":1562,"url":24,"identifiers":1563},"10.1152\u002Fphysiolgenomics.00182.2003",{"doi":1562},{"id":24,"text":1565,"url":24,"identifiers":1566},"10.1002\u002F1098-1136(200010)32:1\u003C42::AID-GLIA40>3.0.CO;2-3",{"doi":1565},{"id":24,"text":1568,"url":24,"identifiers":1569},"10.1016\u002FS0039-6257(96)80066-X",{"doi":1568},{"id":24,"text":1571,"url":24,"identifiers":1572},"10.1085\u002Fjgp.20028597",{"doi":1571},{"id":24,"text":1574,"url":24,"identifiers":1575},"10.1167\u002Fiovs.04-0535",{"doi":1574},{"id":24,"text":1577,"url":24,"identifiers":1578},"10.1093\u002Fhmg\u002F8.12.2221",{"doi":1577},{"id":1580,"createTime":1581,"updateTime":1581,"relativeEntities":1582,"slug":1583,"properties":1584,"entityType":164,"verifyStatus":165,"verifyTime":1581,"verifyNote":166,"syncStatus":23,"languages":1600,"translateLanguages":24,"viewCount":25,"primaryUrl":1601,"fullTextUrl":24,"authors":1602,"publicationType":282,"publisherRelationship":1664,"citationCount":1701,"citationInfo":1702,"publishDate":1714,"publishYear":1715,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":24,"openAccess":24,"references":1716,"isForceReanalyzing":777},"4b848630-ece2-453a-94e5-131a3deb110f","2025-02-07T16:37:54.998+00:00",[],"The-Mitochondrial-Proteome-and-Human-Disease",{"mag":1585,"keywords":1587,"pmc":1588,"openalex":1590,"abstract":1592,"title":1594,"pm":1596,"doi":1598},{"VOID":1586},"2624338235",{},{"VOID":1589},"4397899",{"VOID":1591},"W2624338235",{"EN":1593},"\u003Cjats:p> For nearly three decades, the sequence of the human mitochondrial genome (mtDNA) has provided a molecular framework for understanding maternally inherited diseases. However, the vast majority of human mitochondrial disorders are caused by nuclear genome defects, which is not surprising since the mtDNA encodes only 13 proteins. Advances in genomics, mass spectrometry, and computation have only recently made it possible to systematically identify the complement of over 1,000 proteins that comprise the mammalian mitochondrial proteome. Here, we review recent progress in characterizing the mitochondrial proteome and highlight insights into its complexity, tissue heterogeneity, evolutionary origins, and biochemical versatility. We then discuss how this proteome is being used to discover the genetic basis of respiratory chain disorders as well as to expand our definition of mitochondrial disease. 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Recombination events, however, are also accompanied by short-scale, unidirectional exchanges known as gene conversion in the neighborhood of the initiating double-strand break. A large body of evidence suggests that gene conversion is GC-biased in many eukaryotes, including mammals and human. AT\u002FGC heterozygotes produce more GC- than AT-gametes, thus conferring a population advantage to GC-alleles in high-recombining regions. This apparently unimportant feature of our molecular machinery has major evolutionary consequences. Structurally, GC-biased gene conversion explains the spatial distribution of GC-content in mammalian genomes—the so-called isochore structure. Functionally, GC-biased gene conversion promotes the segregation and fixation of deleterious AT → GC mutations, thus increasing our genomic mutation load. Here we review the recent evidence for a GC-biased gene conversion process in mammals, and its consequences for genomic landscapes, molecular evolution, and human functional genomics. \u003C\u002Fjats:p>",{"EN":2106},"Biased Gene Conversion and the Evolution of Mammalian Genomic 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The low false-positive rate of NIPT, which reduces unnecessary prenatal invasive diagnostic procedures, has led to broad clinician and patient adoption. We discuss the ethical, legal, and social issues raised by rapid and global dissemination of NIPT. The number of women using NIPT is anticipated to expand, and the number of conditions being tested for will continue to increase as well, raising concerns about the routinization of testing and negative impacts on informed decision making. Ensuring that accurate and balanced information is available to all pregnant women and that access to NIPT is equitable will require policy guidance from regulators, professional societies, and payers. Empirical evidence about stakeholders' perspectives and experiences will continue to be essential in guiding policy development so that advances in NIPT can be used effectively and appropriately to improve prenatal care.\u003C\u002Fjats:p>",{"EN":3484},"Noninvasive Prenatal Genetic Testing: Current and Emerging Ethical, Legal, and Social Issues",{"VOID":3486},"26322648",{"VOID":3488},"10.1146\u002Fannurev-genom-090314-050000",[168],"https:\u002F\u002Fwww.annualreviews.org\u002Fdoi\u002F10.1146\u002Fannurev-genom-090314-050000",[3492,3513,3534,3553,3574],{"id":3493,"sortIndex":959,"researcher":24,"roles":3494,"affiliations":3495,"properties":3506},"ac2b6b31-0e47-4d02-9627-14dc7ff83cfd",[],[3496],{"id":3497,"sortIndex":25,"affiliation":3498,"properties":24},"a8d9557a-b3d3-4b4b-a112-b6a485ba7f68",{"id":3499,"createTime":3500,"updateTime":3500,"relativeEntities":3501,"slug":3502,"properties":3503,"entityType":61,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"ef564a6d-26ad-4ca1-816c-9cd663159f9e","2024-12-14T13:36:27.449+00:00",[],"Duke-Global-Health-Institute-Duke-University-Durham-North-Carolina-27710-",{"title":3504},{"EN":3505},"Duke Global Health Institute, Duke University, Durham, North Carolina 27710;",{"openalex":3507,"orcid":3509,"title":3511},{"VOID":3508},"A5102784696",{"VOID":3510},"https:\u002F\u002Forcid.org\u002F0000-0002-9894-3263",{"EN":3512},"Subhashini Chandrasekharan",{"id":3514,"sortIndex":125,"researcher":24,"roles":3515,"affiliations":3516,"properties":3527},"a1614b54-9bef-423e-a0e1-139ec2a5bbc2",[],[3517],{"id":3518,"sortIndex":25,"affiliation":3519,"properties":24},"cb46dcb6-3148-4879-a6ed-91064afc0cbb",{"id":3520,"createTime":3521,"updateTime":3521,"relativeEntities":3522,"slug":3523,"properties":3524,"entityType":61,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"ff4f9f77-df6b-46d4-9f21-db9a2e15a0b4","2024-12-14T13:36:27.437+00:00",[],"Institute-for-Health-and-Aging-University-of-California-San-Francisco-California-94143",{"title":3525},{"EN":3526},"Institute for Health and Aging, University of California, San Francisco, California 94143",{"openalex":3528,"orcid":3530,"title":3532},{"VOID":3529},"A5014943413",{"VOID":3531},"https:\u002F\u002Forcid.org\u002F0000-0001-6631-828X",{"EN":3533},"Marsha Michie",{"id":3535,"sortIndex":124,"researcher":24,"roles":3536,"affiliations":3537,"properties":3548},"e1ed0279-30c2-42f2-a1ad-b9686b182d32",[],[3538],{"id":3539,"sortIndex":25,"affiliation":3540,"properties":24},"cec734ee-671d-408a-9bfc-b827ba8010ee",{"id":3541,"createTime":3542,"updateTime":3542,"relativeEntities":3543,"slug":3544,"properties":3545,"entityType":61,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"420f2aff-6e28-4a98-99e2-029c74213426","2024-12-14T13:36:27.425+00:00",[],"Stanford-Center-for-Biomedical-Ethics-Stanford-University-Stanford-California-94305",{"title":3546},{"EN":3547},"Stanford Center for Biomedical Ethics, Stanford University, Stanford, California 94305",{"openalex":3549,"title":3551},{"VOID":3550},"A5111533772",{"EN":3552},"Stephanie A. 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ObGyn, 6, 7",{},{"id":24,"text":4236,"url":24,"identifiers":4237},"10.1054\u002Fmidw.2002.0316",{"doi":4236},{"id":24,"text":4239,"url":24,"identifiers":4240},"10.1007\u002Fs10897-012-9545-3",{"doi":4239},{"id":24,"text":4242,"url":24,"identifiers":4243},"10.1002\u002Fpd.3946",{"doi":4242},{"id":4245,"createTime":4246,"updateTime":4246,"relativeEntities":4247,"slug":4248,"properties":4249,"entityType":164,"verifyStatus":165,"verifyTime":4246,"verifyNote":166,"syncStatus":23,"languages":4263,"translateLanguages":24,"viewCount":25,"primaryUrl":4264,"fullTextUrl":24,"authors":4265,"publicationType":282,"publisherRelationship":4304,"citationCount":4340,"citationInfo":4341,"publishDate":2740,"publishYear":2741,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":24,"openAccess":24,"references":4344,"isForceReanalyzing":777},"f278f2ec-df05-4391-b105-98fcfbfaa629","2024-09-17T12:47:57.143+00:00",[],"H-scp-UMAN-scp-M-scp-IGRATIONS-AND-scp-P-scp-OPULATION-scp-S-scp-TRUCTURE-scp-What-We-Know-and-Why-it-Matters",{"mag":4250,"keywords":4252,"openalex":4253,"abstract":4255,"title":4257,"pm":4259,"doi":4261},{"VOID":4251},"1830462044",{},{"VOID":4254},"W1830462044",{"EN":4256},"\u003Cjats:p> ▪ Abstract  The increasingly obvious medical relevance of human genetic variation is fueling the development of a rich interface between medical genetics and the study of human genetic history. A key feature of this interface is a step increase in the size and diversity of genetic data sets, permitting a range of new questions to be addressed concerning our evolutionary history. Similarly, methodologies first developed to study genetic history are being tailored to address medical challenges, including mapping genes that influence diseases and variable drug reactions. In this paper we do not attempt a comprehensive review of human genetic history. Rather we briefly outline some of the complications and challenges in the study of human genetic history, drawing particular attention to new opportunities created by the explosive growth in genetic information and technologies. First we discuss the complexity of human migration and demographic history, taking both a genetic and archaeological perspective. Then we show how these apparently academic issues are becoming increasingly important in medical genetics, focusing on association studies, the common disease\u002Fcommon variant hypothesis, the evaluation of variable drug response, and inferences about gene function from patterns of genetic variation. Finally we describe some of the inferential approaches available for interpreting human genetic variation, focusing both on current limitations and future developments. \u003C\u002Fjats:p>",{"EN":4258},"H\u003Cscp>UMAN\u003C\u002Fscp> M\u003Cscp>IGRATIONS AND\u003C\u002Fscp> P\u003Cscp>OPULATION\u003C\u002Fscp> S\u003Cscp>TRUCTURE\u003C\u002Fscp>: What We Know and Why it Matters",{"VOID":4260},"12142358",{"VOID":4262},"10.1146\u002Fannurev.genom.3.022502.103200",[168],"https:\u002F\u002Fwww.annualreviews.org\u002Fdoi\u002F10.1146\u002Fannurev.genom.3.022502.103200",[4266,4287],{"id":4267,"sortIndex":25,"researcher":24,"roles":4268,"affiliations":4269,"properties":4280},"b8b079a8-7aa4-47a2-9fdf-12809ea9839c",[],[4270],{"id":4271,"sortIndex":25,"affiliation":4272,"properties":24},"b6b7dbd6-eda9-4df9-939f-11ff662b3a5c",{"id":4273,"createTime":4274,"updateTime":4274,"relativeEntities":4275,"slug":4276,"properties":4277,"entityType":61,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"c1359623-2a97-45df-8e8a-d3a31e939a3c","2024-09-17T12:47:57.197+00:00",[],"Department-of-Biology-University-College-London-Darwin-Building-London-WC1E-6BT-United-Kingdom-",{"title":4278},{"EN":4279},"Department of Biology, University College London, Darwin Building, London WC1E 6BT, United Kingdom.",{"openalex":4281,"orcid":4283,"title":4285},{"VOID":4282},"A5024558351",{"VOID":4284},"https:\u002F\u002Forcid.org\u002F0000-0002-1111-2820",{"EN":4286},"David B. 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London: Wiley",{},{"id":4834,"createTime":4835,"updateTime":4835,"relativeEntities":4836,"slug":4837,"properties":4838,"entityType":164,"verifyStatus":165,"verifyTime":4852,"verifyNote":166,"syncStatus":23,"languages":4853,"translateLanguages":24,"viewCount":25,"primaryUrl":4854,"fullTextUrl":24,"authors":4855,"publicationType":282,"publisherRelationship":4899,"citationCount":129,"citationInfo":4936,"publishDate":4940,"publishYear":4941,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":24,"openAccess":24,"references":4942,"isForceReanalyzing":777},"38089a38-e488-478d-b9b8-c35acd02bf23","2024-10-01T12:09:54.036+00:00",[],"Sequence-Divergence-Functional-Constraint-and-Selection-in-Protein-Evolution",{"mag":4839,"keywords":4841,"openalex":4842,"abstract":4844,"title":4846,"pm":4848,"doi":4850},{"VOID":4840},"2115759361",{},{"VOID":4843},"W2115759361",{"EN":4845},"\u003Cjats:p> The genome sequences of multiple species has enabled functional inferences from comparative genomics. A primary objective is to infer biological functions from the conservation of homologous DNA sequences between species. A second, more difficult, objective is to understand what functional DNA sequences have changed over time and are responsible for species' phenotypic differences. The neutral theory of molecular evolution provides a theoretical framework in which both objectives can be explicitly tested. Development of statistical tests within this framework has provided insight into the evolutionary forces that constrain and in some cases change DNA sequences and the resulting patterns that emerge. In this article, we review recent work on how functional constraint and changes in protein function are inferred from protein polymorphism and divergence data. We relate these studies to our understanding of the neutral theory and adaptive evolution. \u003C\u002Fjats:p>",{"EN":4847},"Sequence Divergence, Functional Constraint, and Selection in Protein Evolution",{"VOID":4849},"14527302",{"VOID":4851},"10.1146\u002Fannurev.genom.4.020303.162528","2024-10-01T12:09:54.035+00:00",[168],"https:\u002F\u002Fwww.annualreviews.org\u002Fdoi\u002F10.1146\u002Fannurev.genom.4.020303.162528",[4856,4878],{"id":4857,"sortIndex":124,"researcher":24,"roles":4858,"affiliations":4859,"properties":4871},"06576036-b238-40b6-8e56-74a758f4d4ce",[],[4860],{"id":4861,"sortIndex":25,"affiliation":4862,"properties":24},"9606a093-1713-4fb0-a50e-026cb3953e2f",{"id":4863,"createTime":4864,"updateTime":4865,"relativeEntities":4866,"slug":4867,"properties":4868,"entityType":61,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"cb4d45a6-7c63-4fb6-8139-2547863f2f8e","2024-01-11T18:56:27.524+00:00","2024-11-26T13:07:13.418+00:00",[],"Department-of-Ecology-and-Evolution-University-of-Chicago-Chicago-Illinois-60637",{"title":4869},{"VI":4870},"Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, 60637",{"openalex":4872,"orcid":4874,"title":4876},{"VOID":4873},"A5051675346",{"VOID":4875},"https:\u002F\u002Forcid.org\u002F0000-0001-7263-4238",{"EN":4877},"Chung‐I Wu",{"id":4879,"sortIndex":25,"researcher":24,"roles":4880,"affiliations":4881,"properties":4892},"07c1c81f-1819-4f93-8f5c-57f9af19c58b",[],[4882],{"id":4883,"sortIndex":25,"affiliation":4884,"properties":24},"050a2a9c-7011-4d21-a96e-7f98a9c208f9",{"id":4885,"createTime":4886,"updateTime":4886,"relativeEntities":4887,"slug":4888,"properties":4889,"entityType":61,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"1452c521-71c1-4242-9b12-bc7cb7246c42","2024-10-01T12:09:54.052+00:00",[],"Department-of-Genome-Sciences-Lawrence-Berkeley-National-Laboratory-Berkeley-California-94720-",{"title":4890},{"EN":4891},"Department of Genome Sciences, Lawrence Berkeley National Laboratory, Berkeley, California 94720;",{"openalex":4893,"orcid":4895,"title":4897},{"VOID":4894},"A5014443770",{"VOID":4896},"https:\u002F\u002Forcid.org\u002F0000-0003-1893-877X",{"EN":4898},"Justin C. 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